Lycium barbarum Polysaccharides Promote Maturity of Murine Dendritic Cells through Toll-Like Receptor 4-Erk1/2-Blimp1 Signaling Pathway.

Lycium barbarum Polysaccharides Promote Maturity of Murine Dendritic Cells through Toll-Like Receptor 4-Erk1/2-Blimp1 Signaling Pathway.
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枸杞多糖通过Toll样受体4-Erk1/2-Blimp1信号通路促进小鼠树突状细胞成熟

DOI:
10.1155/2020/1751793
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发表时间:
2020
影响因子:
4.1
通讯作者:
Su C
Su C
中科院分区:
医学3区
文献类型:
--
作者:
Duan X;Lan Y;Zhang X;Hou S;Chen J;Ma B;Xia Y;Su C

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以往的研究表明,中药枸杞多糖(LBP)可以促进未成熟树突状细胞(DCs)的成熟。然而,LBP工作的分子机制尚未阐明。我们发现LBP可以诱导DCs成熟,主要表现为MHCII和共刺激分子(CD 80,CD 86)的上调,以及IL-6和IL-4的产生。此外,我们发现LBP可以增加TLR 4,p38,Erk 1/2,JNK和Blimp 1信号分子的mRNA和蛋白表达。更有趣的是,Toll样受体4抑制剂Resatorvid(TAK 242)阻断后,TLR 4、Erk 1/2和Blimp 1的mRNA和蛋白表达显著降低,而p38和JNK的表达没有变化。然后,我们发现分别用p38抑制剂(SB 203580)、Erk抑制剂(PD 98059)和JNK抑制剂(SP 603580)阻断后,Blimp 1蛋白表达显著降低;用Blimp 1-siRNA下调Blimp 1后,IL-6的产生减少。结论:LBP诱导DCs成熟可能是通过TLR 4-Erk 1/2-Blimp 1信号通路而不是JNK/p38-Blimp 1信号通路。本研究结果为深入了解枸杞多糖激活小鼠DCs的分子机制提供了新的证据。
In previous studies, Lycium barbarum polysaccharides (LBP), a traditional Chinese medicine, can promote immature dendritic cells (DCs) to mature. However, the molecular mechanisms by which LBP works are not yet elucidated. Here, we found that LBP can induce DCs maturation, which is mainly characterized by the upregulation of MHCII and costimulatory molecules (CD80, CD86), and increase the production of IL-6 and IL-4. Furthermore, we found that LBP could increase the mRNA and protein expression of TLR4, p38, Erk1/2, JNK, and Blimp1 signal molecules. More interestingly, after blocking by Toll-like receptor 4 inhibitor, Resatorvid (TAK 242), the mRNA and protein expression of TLR4, Erk1/2, and Blimp1 was significantly decreased while the expression of p38 and JNK has not changed. Then, we found that after blocking by p38 inhibitor (SB203580), Erk inhibitor (PD98059), and JNK inhibitor (SP603580) separately, Blimp1 protein expression was significantly reduced; after downregulating Blimp1 by Blimp1-siRNA, the production of IL-6 was reduced. In conclusion, our results indicate that LBP can induce maturation of DCs through the TLR4-Erk1/2-Blimp1 signal pathway instead of the JNK/p38-Blimp1 pathway. Our findings may provide a novel evidence for understanding the molecular mechanisms of LBP on activating murine DCs.
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